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Alexandra Traverse-Glehen,
Emmanuel Bachy,
Lucile Baseggio,
Evelyne Callet-Bauchu,
Sophie Gazzo,
Aurélie Verney,
Sandrine Hayette,
Laurent Jallades,
Martine Ffrench,
Gilles Salles, Bertrand Coiffier,
Pascale Felman,
Francoise Berger
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ABSTRACT: To describe 76 cases of splenic marginal zone lymphoma (SMZL), including correlations with clinical and other characteristics.
Patients were predominantly female, with a median age of 62 years. The main clinical presentation was splenomegaly, except for eight cases presenting with evolution of autoimmune disorders or spontaneous splenic rupture. White pulp infiltration was nodular, with a monophasic (42%) or biphasic (53%) pattern, and associated diffuse or nodular infiltration of the red pulp, except for four cases which had atrophic white pulp. Plasmacytic differentiation and the MYD88 L265P mutation were observed in 18% and 5% of the cases, respectively. Histological progression was considered in cases with a significant association of large cells with Ki67 > 30% and macronodular architecture (P = 0.001). Other significant correlations were found between del7q (44%) and del6q (17%) (P = 0.018), IGHV1-2*04 segment usage (35%) (P = 0.001) and unmutated IGHV (39%) (P = 0.019), and between CD5 expression (27%) and higher lymphocytosis (P = 0.002). Patients requiring intensive chemotherapy after splenectomy because of clinical and/or histological progression had significantly shorter overall survival (P = 0.012).
We report the histological spectrum of SMZL, and discuss the differential diagnosis and requirement for molecular and cytogenetic analysis in atypical cases.
Histopathology 05/2013; 62(6):876-93. · 3.08 Impact Factor
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Bertrand Coiffier,
Weimin Li,
Erin D Henitz,
Jayaprakash Karkera,
Reyna Favis,
Dana Gaffney,
Alice Shapiro,
Panteli Theocharous,
Yusri Elsayed,
Helgi van de Velde, [......],
Adriana Teixeira,
Joanna Romejko-Jarosinska,
Sven de Vos,
Michael Crump,
Ofer Shpilberg,
Pier Luigi Zinzani,
Andrew Cakana,
Dixie-Lee Esseltine,
George Mulligan,
Deborah Ricci
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ABSTRACT: PURPOSE: Identify subgroups of relapsed/refractory follicular lymphoma patients deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase 3 LYM-3001 study. EXPERIMENTAL DESIGN: 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary endpoint was PFS; this pre-specified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for four proteins and eight genes. RESULTS: In initial pair-wise analyses, using individual SNP genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair (PSMB1 P11A G allele, low CD68 expression [≤50 CD68-positive cells], population frequency: 43.6%), median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next anti-lymphoma therapy longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. CONCLUSIONS: Patients with PSMB1 P11A (G allele) and low CD68 expression appeared to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab.
Clinical Cancer Research 04/2013; · 7.74 Impact Factor
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Leukemia & lymphoma 03/2013; · 2.40 Impact Factor
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Fabrice Jardin,
Marie Hélène Delfau-Larue,
Thierry Jo Molina,
Christiane Copie-Bergman,
Josette Brière,
Tony Petrella,
Danielle Canioni,
Bettina Fabiani,
Jean-Philippe Jais,
Martin Figeac, [......],
Sylvain Mareschal,
Gilles André Salles, Bertrand Coiffier,
Richard Delarue,
Frédéric Peyrade,
André Bosly,
Marc André,
Nicolas Ketterer,
Corinne Haioun,
Hervé Tilly
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ABSTRACT: Abstract Elevated serum free light chains (FLC) have been associated with unfavorable prognostic in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to determine the clinical relevance of a quantitative assessment of intact circulating immunoglobulin (Ig), using serum Ig heavy chain/light chain pair (HLC) measurements in DLBCL patients. FLC and HLC were measured in 409 serums of DLBCL patients included in the LNH03-B clinical trial program of the GELA. Patients with an abnormal IgMκ/IgMλ ratio or an abnormal FLC ratio more frequently displayed adverse clinical characteristics. Patients with abnormal IgMκ/IgMλ ratios had inferior PFS and OS as compared to patients with normal ratio in the overall cohort (5y-PFS CI95% 44.9 % vs. 69.3%, p =0.0003 and 5y-0S CI95% 50.8% vs. 78.1%, p =0.0003) and in the R-CHOP cohort (5y-0S 43.5% vs. 70.3%, p =0.003). In multivariate analysis including elevated FLC/HLC and IPI, an abnormal IgMκ/IgMλ ratio (HR =1.54, CI95% 1.03-2.3, p =0.03) remained predictive of shorter progression-free survival. Gene expression profile experiments and immunohistochemistry indicate that this measurement is at least partially related to the tumor cell secretion. Both elevated serum FLC and an abnormal IgMκ/IgMλ ratio are associated with unfavorable outcomes in DLBCL patients treated by R-CHOP.
Leukemia & lymphoma 01/2013; · 2.40 Impact Factor
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Emanuele Zucca,
Annarita Conconi,
Daniele Laszlo,
Armando López-Guillermo,
Reda Bouabdallah, Bertrand Coiffier,
Catherine Sebban,
Fabrice Jardin,
Umberto Vitolo,
Franck Morschhauser,
Stefano A Pileri,
Christiane Copie-Bergman,
Elias Campo,
Andrew Jack,
Irene Floriani,
Peter Johnson,
Maurizio Martelli,
Franco Cavalli,
Giovanni Martinelli,
Catherine Thieblemont
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ABSTRACT: PURPOSEApart from localized gastric disease, there is no consensus on standard initial treatment of mucosa-associated lymphoid tissue lymphoma. The IELSG-19 study (Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in MALT Lymphoma) was launched to compare chlorambucil alone versus chlorambucil plus rituximab in patients not previously given systemic anticancer therapy. PATIENTS AND METHODS
Patients not responding to or not suitable for local therapy were eligible. In arm A, chlorambucil was given daily 6 mg/m(2) orally (PO) for 6 weeks. Responding patients and those with stable disease continued to be given daily chlorambucil 6 mg/m(2) PO for 14 consecutive days every 28 days for four cycles. In arm B, intravenous rituximab 375 mg/m(2) per day was added on days 1, 8, 15, 22, 56, 84, 112, and 140. After completion of the planned accrual, the protocol was amended to introduce a third arm with rituximab alone. We report the planned final analysis of the first two arms (113 patients in arm A and 114 in arm B).ResultsAt a median follow-up of 62 months, the 5-year event-free survival (EFS) was significantly better for the patients treated in arm B (68% v 50%; P = .002) who, despite similar overall response rates (90% v 87%), achieved a higher complete remission rate (78% v 65%; P = .025). Progression-free survival was also improved but it did not reach statistical significance (P = .057). Five-year overall survival (OS) was 89% in both arms. Both treatments were well tolerated without unexpected toxicities. CONCLUSION
Both treatments were active; the better response rate and EFS obtained with the addition of rituximab did not translate into improved OS.
Journal of Clinical Oncology 01/2013; · 18.37 Impact Factor
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Luis Fayad,
Fritz Offner,
Mitchell R Smith,
Gregor Verhoef,
Peter Johnson,
Jonathan L Kaufman,
Ama Rohatiner,
Anjali Advani,
James Foran,
Georg Hess, Bertrand Coiffier,
Myron Czuczman,
Eva Giné,
Simon Durrant,
Michelle Kneissl,
Kenneth T Luu,
Steven Y Hua,
Joseph Boni,
Erik Vandendries,
Nam H Dang
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ABSTRACT: PURPOSEInotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20(+)/CD22(+) B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODSA dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles.ResultsIn all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m(2)) was confirmed to be the same as that for single-agent INO (1.8 mg/m(2)). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. CONCLUSIONR-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20(+)/CD22(+) B-cell NHL.
Journal of Clinical Oncology 01/2013; · 18.37 Impact Factor
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ABSTRACT: The aim of this study was to verify whether pretreatment plasma levels of vascular endothelial growth factor (VEGF) correlate with prognosis and survival of patients with diffuse large B-cell lymphoma (DLBCL). Plasma VEGF levels were assessed at the time of diagnosis in 157 DLBCL patients treated with anthracycline-based chemotherapy. Plasma VEGF levels greater than or equal to the highest quartile (high VEGF levels) were associated with lower probability of a complete remission achievement (odds ratio 0.3; 95 % confidence interval [CI]: 0.1-0.6; p = 0.002) in univariate as well as in multivariate analysis (p = 0.04). The estimated 3-year progression-free survival (PFS) rate of patients with high VEGF levels was 31.7 % (95 % CI 17-51) compared to the 62.5 % 3-year PFS rate (95 % CI 53-71; p = 0.0004) in the patients with lower values. The former group of patients demonstrated an estimated 3-year overall survival (OS) rate of 47.1 % (95 % CI 30-65) in contrast to the 3-year OS rate of 64.3 % (95 % CI 54-73; p = 0.02) in the latter. In multivariate analysis, the high VEGF level retained its independent impact on shorter PFS (p = 0.02). Our results suggest that VEGF plays an important role in the clinical course of DLBCL. VEGF may be a useful marker for selecting the patients for whom new treatment approaches, especially those based on VEGF inhibitors, could be recommended.
Archivum Immunologiae et Therapiae Experimentalis 01/2013; · 2.54 Impact Factor
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ABSTRACT: Prognosis of diffuse large B-cell lymphoma (DLBCL) has considerably improved during the last decade, mainly due to the addition of rituximab to chemotherapy. However, a significant proportion of patients still experience primary refractory disease or short-term relapses, conferring poor survival. Thus, achieving first-line complete remission is of major importance, especially in young and fit patients. Current strategies are based on the age-adapted International Prognostic Index, which separates patients into three prognostic subgroups (low-risk, intermediate-risk, and high-risk). However, it is based only on clinical variables, and we have learned from daily practice that there remains a marked heterogeneity within each subgroup. Recently, biological prognostic factors have emerged, and should now be part of initial evaluation to guide treatment. Among those, so-called double-hit DLBCL with deregulation of both MYC and BCL2 genes usually follows a particularly aggressive course and should be treated more intensively. But for many other patients, the indication of high-dose therapy rather than immunochemotherapy alone remains controversial. In these cases, the interest of an early (18)F fluoro-2-deoxy-d-glucose positron emission tomography evaluation-based strategy is now being assessed in ongoing clinical trials. Moreover, other strategies to improve response and survival consist in adding novel agents to standard chemotherapy. In this field, newly developed anti-CD20 monoclonal antibodies and immunomodulatory drugs could be of particular interest during induction therapy to optimize the quality of response, but also in maintenance treatment, in order to decrease the risk of relapse. Only well-conducted clinical trials will be able to resolve all these issues. Therefore, physicians should be encouraged, as far as possible, to propose them to their patients.
OncoTargets and Therapy 01/2013; 6:289-96. · 1.26 Impact Factor
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Vincent Ribrag,
Hervé Tilly,
Olivier Casasnovas,
André Bosly,
Reda Bouabdallah,
Richard Delarue,
François Boue,
Dominique Bron,
Pierre Feugier,
Corinne Haioun,
Firtz Offner, Bertrand Coiffier
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ABSTRACT: PURPOSE: Bortezomib has previously demonstrated activity in indolent lymphomas including follicular lymphoma with response rate ranging from 13% to 56%. However, the optimal schedule of bortezomib remains to be investigated in follicular lymphoma. EXPERIMENTAL DESIGN: We conducted a randomised phase II study where patients with follicular lymphoma in relapse or refractory receive either bortezomib 1.5mg/m(2) biweekly on days 1, 4, 8 and 11 of a 21-day cycle (arm A) or 1.6mg/m(2) weekly on days 1, 8, 15 and 22 of a 35-day cycle (arm B). An interim analysis was planned after 15 fully evaluable patients randomised in each treatment arm. If only five subjects or fewer respond, the treatment arm was concluded to be ineffective and was closed to inclusion. RESULTS: Eighty-seven patients were included in the trial. Arm B was closed to inclusion after interim analysis. 15/50 patients (30%) in arm A and 8/37 patients (22%) in arm B achieved a response. Median duration of response was 16 and 15 months for arms A and B, respectively. Most drug-related adverse events (AEs) (all grades, all cycles) were mild. CONCLUSION: This study demonstrates tolerability and durable clinical benefit of bortezomib when given at 1.5mg/m(2) biweekly. Despite a higher response rate in the biweekly arm, no major difference in patient's outcome was observed between the two arms in the final analysis.
European journal of cancer (Oxford, England: 1990) 12/2012; · 4.12 Impact Factor
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Pier Luigi Zinzani,
Nuriet K Khuageva,
Huaqing Wang,
Bernardo Garicochea,
Jan Walewski,
Achiel Van Hoof,
Pierre Soubeyran,
Dolores Caballero,
Rena Buckstein,
Dixie-Lee Esseltine,
Panteli Theocharous,
Christopher Enny,
Eugene Zhu,
Yusri A Elsayed, Bertrand Coiffier
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ABSTRACT: BACKGROUND: The randomized phase 3 LYM3001 trial in relapsed follicular lymphoma (FL) demonstrated higher overall (ORR) and complete response (CR) rates and prolonged progression-free survival (PFS) with bortezomib-rituximab versus rituximab. We report findings in high-risk patients (FL International Prognostic Index [FLIPI] score [greater than or equal to]3, and high tumor burden by modified Groupe d'Etude des Lymphomas Folliculaires [GELF] criteria). METHODS: Patients aged [greater than or equal to]18 years with grade 1/2 FL, [greater than or equal to]1 measurable lesion, and documented relapse or progression following prior therapy, rituximab-naive or rituximab-sensitive, were enrolled at 164 centers in 29 countries across Europe, the Americas, and Asia-Pacific. Patients were randomized (1:1) to five 5-week cycles of bortezomib-rituximab (bortezomib 1.6 mg/m2, days 1, 8, 15, and 22, all cycles; rituximab 375 mg/m2, days 1, 8, 15, and 22, cycle 1, and day 1, cycles 2-5; N=336) or rituximab alone (N=340). Randomization was stratified by FLIPI score, prior rituximab, time since last dose of anti-lymphoma therapy, and geographical region. The primary endpoint of the study was PFS. RESULTS: 103 bortezomib-rituximab and 98 rituximab patients had high-risk FL. The ORR was 59% versus 37% (p=0.002), the CR/CRu rate was 13% versus 6% (p=0.145), and the durable response rate was 45% versus 26% (p=0.008) with bortezomib-rituximab versus rituximab. Median PFS was 9.5 versus 6.7 months (hazard ratio [HR] 0.667, p=0.012) with bortezomibrituximab versus rituximab; median time to progression was 10.9 versus 6.8 months (HR 0.656, p=0.009); median time to next anti-lymphoma treatment was 14.8 versus 9.1 months (HR 0.762, p=0.103); and the 1-year Overall Survival rate was 83.1% versus 76.6%. Overall, 51% of bortezomib-rituximab and 32% of rituximab patients reported grade [greater than or equal to]3 adverse events, including neutropenia (18%, 6%), anemia (4%, 5%), diarrhea (8%, 0%), thrombocytopenia (5%, 2%), and sensory neuropathy (1%, 0%). CONCLUSIONS: High-risk FL patients treated with bortezomib-rituximab had significantly higher ORR and longer PFS than patients receiving rituximab alone, with greater clinical benefit than in the overall study population; additional toxicity was acceptable and did not affect treatment feasibility. Trial registration The phase 3 LYM3001 trial is registered with ClinicalTrials.gov, with the identifier NCT00312845.
Journal of Hematology & Oncology 10/2012; 5(1):67. · 3.99 Impact Factor
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David Sibon,
Marion Fournier,
Josette Brière,
Laurence Lamant,
Corinne Haioun, Bertrand Coiffier,
Serge Bologna,
Pierre Morel,
Jean Gabarre,
Olivier Hermine,
Anne Sonet,
Christian Gisselbrecht,
Georges Delsol,
Philippe Gaulard,
Hervé Tilly
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ABSTRACT: PURPOSESystemic anaplastic large-cell lymphoma (ALCL) is a T-cell lymphoma, whose anaplastic lymphoma kinase (ALK) expression varies according to age. Long-term outcomes of chemotherapy-treated adults are not definitively established and should be evaluated. PATIENTS AND METHODS
Patients treated in three Groupe d'Étude des Lymphomes de l'Adulte prospective clinical trials with confirmed systemic ALCL after immunohistopathologic review and defined ALK expression status were analyzed.ResultsAmong the 138 adult patients with ALCL, 64 (46%) were ALK positive, and 74 (54%) were ALK negative. Median follow-up was 8 years. At diagnosis, significantly more patients younger than 40 years old were ALK positive than ALK negative (66% v 23%, respectively; P < .001). Comparing patients with ALK-positive and ALK-negative ALCL, β(2)-microglobulin was ≥ 3 mg/L in 12% and 33% (P = .017); International Prognostic Index was high (score, 3 to 5) in 23% and 48% (P = .03); complete response rates to first-line treatment were 86% and 68% (P = .01); and 8-year overall survival (OS) rates were 82% (95% CI, 69% to 89%) and 49% (95% CI, 37% to 61%), respectively (P < .001). The survival difference mostly affected patients age ≥ 40 years. Multivariate analysis identified β(2)-microglobulin ≥ 3 mg/L (P < .001) and age ≥ 40 years (P = .029), but not ALK status, as prognostic for OS. These two variables distinguished four survival risk groups, with 8-year OS ranging from 84% to 22%. CONCLUSION
Results of this long-term study enabled refinement of the prognosis of adult systemic ALCL, with ALK prognostic value dependent on age, and could provide guidance for eventual treatment adjustment.
Journal of Clinical Oncology 10/2012; · 18.37 Impact Factor
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Massimo Federico,
Thomas Rudiger,
Monica Bellei,
Bharat N Nathwani,
Stefano Luminari, Bertrand Coiffier,
Nancy L Harris,
Elaine S Jaffe,
Stefano A Pileri,
Kerry J Savage,
Dennis D Weisenburger,
James O Armitage,
Nicholas Mounier,
Julie M Vose
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ABSTRACT: PURPOSEThe International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-cell and natural killer (NK) -cell lymphomas. PATIENTS AND METHODS
Angioimmunoblastic T-cell lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated. RESULTS: age ≥ 60 years, stages III to IV disease, lactic dehydrogenase (LDH) > normal, extranodal sites (ENSs) > one, and performance status (PS) ≥ 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age ≥ 60 years, PS ≥ 2, LDH > normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age > 60 years, PS ≥ 2, ENSs > one, B symptoms, and platelet count < 150 × 10(9)/L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P = .0065). CONCLUSIONAITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies.
Journal of Clinical Oncology 08/2012; · 18.37 Impact Factor
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ABSTRACT: In this article, we focused on the role of maintenance therapy in diffuse large B-cell lymphoma (DLBCL).
Treatment with maintenance rituximab after a response to induction therapy appears to be an effective approach to extending response duration. In randomized phase III trials, investigators have reported improved event-free and progression-free survival with maintenance rituximab in patients with newly diagnosed follicular lymphoma.
Rituximab administered as induction or maintenance therapy in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly prolonged event-free survival. However, continued use of rituximab after R-CHOP failed to demonstrate benefit. The necessity of a subsequent dose-intense consolidation or maintenance strategy continues to be an issue. High-dose therapy followed by autologous stem cell transplantation is the treatment of choice for patients with relapsed DLBCL who are still responding to salvage therapy. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in patients with complete remission after autologous transplant may be a useful novel approach capable of eradicating minimal residual disease. However, there are currently no data confirming this hypothesis.
Current opinion in oncology 06/2012; 24(5):461-5. · 4.09 Impact Factor
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Adrien Chauchet,
Anne-Sophie Michallet,
Françoise Berger,
Isabelle Bedgedjian,
Eric Deconinck,
Catherine Sebban,
Daciana Antal,
Hubert Orfeuvre,
Bernadette Corront,
Tony Petrella,
Maya Hacini,
Marie Bouteloup,
Gilles Salles, Bertrand Coiffier
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ABSTRACT: Extranodal nasal-type NK/T-cell lymphoma is a rare and severe disease. Considering the rarity of this lymphoma in Europe, we conducted a multicentric retrospective study on nasal-type NK/T cell lymphoma to determine the optimal induction strategy and identify prognostic factors.
Thirty-six adult patients with nasal-type NK/T-cell lymphoma were recruited and assessed. In total, 80 % of patients were classified as having upper aerodigestive tract NK/T-cell lymphoma (UNKTL) and 20 % extra-upper aerodigestive tract NK/T-cell lymphoma (EUNKTL).
For advanced-stage disease, chemotherapy alone (CT) was the primary treatment (84 % vs. 10 % for combined CT + radiation therapy (RT), respectively), while for early-stage disease, 50 % of patients received the combination of CT + RT and 50 % CT alone. Five-year overall survival (OS) and progression-free survival (PFS) rates were 39 % and 33 %. Complete remission (CR) rates were significantly higher when using CT + RT (90 %) versus CT alone (33 %) (p < 0.0001). For early-stage disease, CR rates were 37 % for CT alone versus 100 % for CT + RT. Quality of response was significantly associated with survival, with 5-year OS being 80 % for CR patients versus 0 % for progressive disease patients (p < 0.01).
Early RT concomitantly or sequentially with CT led to improved patient outcomes, with quality of initial response being the most important prognosticator for 5-year OS.
Journal of Hematology & Oncology 06/2012; 5:27. · 3.99 Impact Factor
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Francine Foss,
Steven M Horwitz, Bertrand Coiffier,
Nancy Bartlett,
Leslie Popplewell,
Barbara Pro,
Lauren C Pinter-Brown,
Andrei Shustov,
Richard R Furman,
Corinne Haioun,
Tony Koutsoukos,
Owen A O'Connor
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ABSTRACT: Transformed mycosis fungoides (tMF) is an aggressive disease with a median survival of 12-24 months. In this retrospective analysis of 12 patients with tMF, treatment with pralatrexate resulted in an objective response of 25% per independent central review and 58% per investigator assessment. Pralatrexate was well tolerated, with no toxicity-related discontinuations, which makes this an additional option for tMF treatment.
Transformed mycosis fungoides (tMF) is an aggressive disease, with poor prognosis and a median survival of 24 months.
In the Pralatrexate in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PROPEL) study, 12 patients with tMF were treated with a median of 10 pralatrexate doses (starting dose of 30 mg/m(2)) administered weekly for 6 weeks in a 7-week cycle. The median number of prior systemic therapies was 3.
This retrospective analysis showed that the objective response rate in this subgroup was 25% (n = 3) per independent central review and 58% (n = 7) per investigator assessment, with this discrepancy likely attributed to challenges with photodocumentation of cutaneous lesions. The median duration of response and the median progression-free survival were 2.2 and 1.7 months, respectively, per central review, whereas median duration of response was 4.4 months, and median progression-free survival was 5.3 months per investigator assessment. Median survival was 13 months. Grade 1-3 mucositis was reported in 7 (58%) patients. Grade 4 adverse events were fatigue (n = 1) and thrombocytopenia (n = 1). Pralatrexate was well tolerated, with no toxicity-related discontinuations.
Based on these results, pralatrexate may be a treatment option for patients with relapsed or refractory tMF.
Clinical lymphoma, myeloma & leukemia 04/2012; 12(4):238-43.
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The Lancet 04/2012; 379(9828):1767-8. · 38.28 Impact Factor
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ABSTRACT: Among splenic lymphomas with circulating cells presenting cytoplasmic projections, a homogeneous clinico-pathological entity has been recently individualized as Splenic Diffuse Red Pulp Lymphomas (SDRPL) and introduced in the provisional "unclassifiable splenic lymphoma" category of the current updated WHO classification until more is known. SDRPL presents characteristic circulating basophilic villous lymphocytes and diffuse infiltration of the splenic red pulp, distinct from Splenic Marginal Zone Lymphoma (SMZL) and Hairy Cell Leukemia (HCL), but reminiscent of HCL-Variant (HCL-V). Series of SDRPL remain sparse in the literature and controversies exist about the relationship with other splenic lymphomas. Distinction of these disorders at diagnosis can be difficult, but an adequate diagnosis is important due to differences in patient management and clinical outcome. Especially, BRAF mutations have been detected in almost all patients with HCL that may have implications for pathogenesis, diagnosis, and targeted therapy. This review will report literature data and discuss the differential diagnosis, particularly with HCL-V.
Discovery medicine 04/2012; 13(71):253-65.
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Zdravko Mitrovic,
Anamarija M Perry,
Junji Suzumiya,
James O Armitage,
Wing Y Au, Bertrand Coiffier,
Harald Holte,
Elaine S Jaffe,
Emili Monserrat,
Sandeep K Rajan,
Kerry J Savage,
Kensei Tobinai,
Julie M Vose,
Dennis D Weisenburger
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ABSTRACT: Lymphopenia is a marker of inferior survival in patients with various malignancies. However, the prognostic significance of lymphopenia in peripheral T-cell lymphoma (PTCL) is unclear. We analyzed the prognostic significance of lymphopenia in 826 patients with different types of PTCL and natural killer/T-cell lymphoma (NKTCL) from the International Peripheral T-cell Lymphoma Project. Lymphopenia was defined as an absolute lymphocyte count of less than 1,000 cells per microliter. The overall frequency of lymphopenia was 35.3%, ranging from 21.1% in ALK(+) anaplastic large cell lymphoma (ALCL) to 47.5% in angioimmunoblastic T-cell lymphoma (AITL). Lymphopenia was independently associated with an inferior overall survival (OS) in patients with the lymphoma type of adult T-cell leukemia/lymphoma (ATLL), with a 2-year OS of 15% versus 40% for those without lymphopenia (P < 0.001). Lymphopenia was also an adverse predictor of survival in PTCL, not otherwise specified, but was associated with other unfavorable prognostic factors. A trend toward inferior survival for lymphopenic patients was also observed in AITL, ALK(-) ALCL and extranasal NKTCL lymphoma, whereas no difference in survival was found in nasal NKTCL, ALK(+) ALCL, or enteropathy-associated T-cell lymphoma. In this study, lymphopenia was identified as a new adverse prognostic factor in the lymphoma type of ATLL.
American Journal of Hematology 03/2012; 87(8):790-4. · 4.67 Impact Factor
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Bertrand Coiffier,
Barbara Pro,
H Miles Prince,
Francine Foss,
Lubomir Sokol,
Matthew Greenwood,
Dolores Caballero,
Peter Borchmann,
Franck Morschhauser,
Martin Wilhelm,
Lauren Pinter-Brown,
Swaminathan Padmanabhan,
Andrei Shustov,
Jean Nichols,
Susan Carroll,
John Balser,
Barbara Balser,
Steven Horwitz
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ABSTRACT: Romidepsin is a structurally unique, potent class 1 selective histone deacetylase inhibitor. The primary objective of this international, pivotal, single-arm, phase II trial was to confirm the efficacy of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).
Patients who were refractory to at least one prior systemic therapy or for whom at least one prior systemic therapy failed received romidepsin at 14 mg/m(2) as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days. The primary end point was the rate of complete response/unconfirmed complete response (CR/CRu) as assessed by an independent review committee.
Of the 131 patients enrolled, 130 had histologically confirmed PTCL by central review. The median number of prior systemic therapies was two (range, one to eight). The objective response rate was 25% (33 of 130), including 15% (19 of 130) with CR/CRu. Patient characteristics, prior stem-cell transplantation, number or type of prior therapies, or response to last prior therapy did not have an impact on response rate. The median duration of response was 17 months, with the longest response ongoing at 34+ months. Of the 19 patients who achieved CR/CRu, 17 (89%) had not experienced disease progression at a median follow-up of 13.4 months. The most common grade ≥ 3 adverse events were thrombocytopenia (24%), neutropenia (20%), and infections (all types, 19%).
Single-agent romidepsin induced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across all major PTCL subtypes, regardless of the number or type of prior therapies. Results led to US Food and Drug Administration approval of romidepsin in this indication.
Journal of Clinical Oncology 02/2012; 30(6):631-6. · 18.37 Impact Factor
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Catherine Thieblemont,
Frederic Davi,
Maria-Elena Noguera,
Josette Brière,
Francesco Bertoni,
Emanuele Zucca,
Alexandra Traverse-Glehen,
Pascale Felman,
Françoise Berger,
Gilles Salles, Bertrand Coiffier
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ABSTRACT: Splenic marginal zone lymphoma (SMZL), along with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and nodal marginal zone lymphoma (NMZL), share a common origin from the "marginal zone." However, these three entities display different clinical characteristics, reflecting probable biological variations according to the organ and cellular origin. Within the past decade, new data have been reported regarding pathogenic mechanisms as well as therapeutic advances. Clinically, SMZL presents as an indolent and disseminated disease at diagnosis, with a specific clinical presentation that includes predominantly splenomegaly, and in half of patients, autoimmune manifestations. Establishing the diagnosis may be difficult, especially distinguishing SMZL from other low-grade lymphomas, such as small B-cell lymphomas; however, recent findings have contributed to a better characterization of the disease, and the criteria for diagnosis have been improved. Therapeutic approaches consist of splenectomy or immunochemotherapy, but there is no consensus regarding the best treatment, except when SMZL is associated with hepatitis C virus infection. In this article, we review the current knowledge on the biological findings, clinical features, and therapeutic approaches for SMZL.
Oncology (Williston Park, N.Y.) 02/2012; 26(2):194-202. · 1.03 Impact Factor
